Numerical sensitivity of trajectories across conformational energy hypersurfaces from geometry optimized molecular orbital calculations: AM1, MNDO, and MINDO/3

Abstract

AbstractThe monocyclic β‐lactam [[4(S)‐methyl‐2‐oxo‐1‐azetidinyl]thia]acetic acid was studied by the semiempirical molecular orbital methods AM1, MNDO, and MINDO/3. Using the reaction coordinate option in the program MOPAC on VAX and Cray X‐MP computers, the potential energy curve was calculated for rotation of the C2‐N1‐S‐C torsional angle in the conformationally flexible side chain while optimizing all other geometrical variables in the molecule. The trajectory taken during geometry optimization was found to be sensitive to the computer, the program version, the convergence criteria, and the degree of code optimization used in the calculation. In order to reduce the likelihood of spurious results, conformational or reaction energy hypersurfaces need to be calculated with the more precise SCF convergence and minimization criteria available in programs for MINDO/3, MNDO, and AM1 calculations. The nitrogen in the model β‐lactam antibiotic is predicted to invert periodically as the dihedral angle to the exocyclic N‐substituent sweeps through 360°.